Basics Of Immunity PDF Fall 2025

Basics of immunity Immunology : Is a branch of medicine and biology that covers the medical study of immune systems in humans, animals and plants.  A large number of the inflammatory conditions treated by oral medicine clinicians are either autoimmune in nature or are influenced b...

Basics of immunity Immunology : Is a branch of medicine and biology that covers the medical study of immune systems in humans, animals and plants.  A large number of the inflammatory conditions treated by oral medicine clinicians are either autoimmune in nature or are influenced by the immune response.  A good understanding of immunology is needed to treat patients receiving immunomodulating agents to comprehend their mechanisms of action and possible side effects. The immune system A multifaceted system whose main function is protection against infection It counteracts insults from the environment Neutralizes foreign or “non-self”-antigens that are expressed by a large variety of microbial agents and some tumors The immune system must be able to perceive Generate produce a Down regulate the antigens as activation variety of inflammatory foreign signals effector proteins process once the that neutralize foreign agent is pathogens or eliminated activate other cells,  For any battle to occur, there should be: Attack Defense versus (antigen) (immunity) It is a substance which The immune when introduced into system reactions the body is able to such as antibodies Produce immunological immunoglobulins responce production What is antigen (Ag)?  It is a substance foreign to the body of high molecular weight when introduced into the body is able to produce immunological response. Antigenic determinant“epitopes” key : Ag should have an antigenic determinant to react with the receptors of the lymphocytes, Initiate the immune reaction  The severity of the immune reaction depends on several factors: Chemical nature: The more the chemical complexity, the more potent the Ag, e.g. synthetic peptides (so that, the homo-polymers are poor immunogens than co-polymers). Dose and route of administration: once the threshold is exceeded, increasing the dose will increase the immune response. Subcutaneous (S.C.) & Intramuscular (I.M.) routes of administration are the safest than Intravenous (I.V.). Genetic constitution: the body response to the antigen varies with the genetic make up. What is hapten??  It is an (incomplete or partial antigen)  Antigen with a small molecular weight, alone has no antigenicity  Most drugs are haptens, but some of them when introduced to the body it combines with body proteins forming a (hapten – protein conjugate) that can provoke an immune response.  What is Antibody? immunoglobulin (Ig)  is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses.  Each tip of the "Y" of an antibody contains a paratope the lock that is specific for one particular epitope the key on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism The antibody Tag a microbe or an infected cell Neutralize the for attack by other parts of the microbe Directly immune system,  The immune response is classified into innate immunity adaptive immunity These two systems are highly coordinated with cross talking signals nonspecific highly specific and targeted immediate takes several days to develop  Innate Immunity :Three main components Physical Complement system barrier Circulating cells Additional aids Normal bacteria flora e.g. symbiotic relationship between lactobacilli and yeast. The body oxygen tension: it limits the growth of anaerobic micro-organisms. The normal rythm of body hormones, so any abnormality in their level or act will increase susceptibility to infection (e.g.; DM & adrenal insuffeciency). Genetic predisposition: certain species are susceptible to particular agents, while others are not. Body temperature pyrexia may function as a protective response against invading microorganisms Phyical barrier  Physical barrier skin Mucous membranes Intact skin & mucous membrane afford a high degree of protection Skin - Indigestible Keratin by microorganisms. - High concentration of salts in drying sweat. - Bactericidal and fungicidal property of sebaceous and sweat glands. Mucous membranes: in the oral cavity  The oral mucosa covered with its mucin layer: Mechanically blocks the penetration of pathogens Fortified by a variety of secreted antimicrobial peptides that kill or limit many organisms  Saliva: Several salivary proteins (such as lactoferrin, lysozyme, and mucins) have:  antimicrobial,  immunomodulatory, properties  anti-inflammatory Other mucosal surfaces: examples Nasal cavity : - Cilia sweeps inhaled particles to oro-pharynx, & then swallowed. - Muco-polysaccharide in nasal secretion & saliva block some viruses Stomach: - Acidic secretion of the stomach destroys most organisms. Urinary system: - Mechanical cleansing & washing action of urine.  Circulating cells Blood is composed of:  Blood cells suspended in Blood plasma.  Plasma: water (92% by volume), protiens, glucose, minerals, hormones, CO2  Haematopoiesis: From the Greek words: Make (Poiesis) & Haem (Blood) i.e to make  The formation of blood cellular components including the cellular constituents of the immune system.  Occurs in the bone marrow  Result of differentiation of a single precursor cell is known as “Pluripotent haemopoietic stem cell” that is capable of giving rise to all blood cell lineages  Self-regulating process with normal target distribution  Maintain a steady state of production balanced with natural senescence and removal.  Pluripotent haemopoietic stem cell Common common lymphoid progenitor myeloid progenitor (Lymphoid stem cell) (Myloid stem cell) B- T- Lymphocytes Lymphocytes Leukocytes Erythocyets Megakaryocytes Cellular component of the blood Platelets: Thrombocytes  Derived from the megakaryocytes  Have no cell nucleus; they are fragments of cytoplasm  Normal range 150.000 to 500 000 /mm3  Clumping at the site of injury of the blood vessel initiating a blood clot formation.  The average life span of circulating platelets is 8 to 9 days Erythrocytes  Red blood corpuscles, Red blood cells (RBCs), Red cells haematids, Erythroid cells  In humans, mature red blood cells are flexible biconcave disks. They lack a cell nucleus and organelles, to accommodate maximum space for hemoglobin  principal means of delivering oxygen (O2) to the body tissues via blood flow through the circulatory system.  Normal range 3.8 To 5.69 (million/mm3)  The average life span about 100–120 days  I- Phagocytic cells and granulocytes Neutrophils B- T- Monocytes Eosinophils Basophils microphages lymphocytes lymphocytes macrophages II- Natural killer III- Dendritic cells. VI- Certain B cells IV- Mast cells Cells of the Innate immunity I- The primary phagocytic cells are In bone marrow macrophages and microphages derived from common myeloid precursor a common myeloid precursor in the bone marrow. In blood circulation Monocytes Neutrophils In tissues Macrophages Microphages  Neutrophils, polymorphonuclear leukocytes (PMNs) multi-lobed nuclei pattern. (Hence their name polymorphonuclear) The nucleus has 3-5 lobes joined by chromatin threads. It is the 1st line of defense, directed quickly to the site of infection activated by bacterial products and other cytokines released during inflammation. Monocytes, tissue Macrophages:  Morphology of monocyte & macrophage is highly variable, they are larger than neutrophils and lymphocytes. Phagocytes functions: Phagocytes have analogous activities however neutrophils move rapidly whereas macrophages move slowly. Destroying & Chemotaxis get rid of the foreign organisms Phagocytosis In human body phagocytes perform 3 main functions Macrophages as killing secretory cells Macrophages as Antigen Presenting Cells   (from chemo- + taxis) is the movement of an organism or entity in response to a chemical stimulus,  cells direct their movements according to certain chemicals (Chemoattractants) in their environment.  Chemoattractants: inorganic or organic substances possessing chemotaxis-inducer effect in motile cells  The concentration of attracting molecules (chemo-attractants) elevated as a result of inflammatory reaction at the site of infection. which steer the phagocytes movement to the inflammation site.  is a protein fragment released from cleavage of complement component C5 by protease C5-convertase such as N-Formylmethionyl-leucyl-phenylalanine, fMLF soluble elements released by the bacteria family of inflammatory mediators produced in leukocytes convey information to either the cell producing them (autocrine signaling) or neighboring cells (paracrine signaling) in order to regulate immune responses.  Pathogens internalization  The phagocytes internalizes foreign material by creating endosomes, using pseudopodia that surround the organism.  Enhanced By: when the material is bound by specific antibody and/or Receptors for the opsonins are complement, (opsonins) present on the neutrophil surface forming a bridge between the cell and organism Opsonized bacterium binds to neutrophils; pseudopodia extend around the bacterium Then eventually meet and fuse to form an enclosed vacuole termed phagosome. Bacterium is engulfed inside a phagosome  The intracellular phagosome can now be fused with granules which release their digestive and toxic contents. : neutrophils form super oxide anions neutrophils contain enzymes that can break & hydrogen peroxide that kill the wall of bacterial cell through enzymatic ingested pathogen. lysis (e.g. Lysozyme  Another major function of foreign material internalization is antigen processing and presentation to lymphocytes to initiate the adaptive immune response.  Macrophages take up antigens to T lymphocytes in a form they can recognize break it into small bounded to specific macrophages fragments. cell surface receptors engulf the to be presented to T- foreign material lymphocytes  Macrophages produce over 30 secreted products e.g.; enzymes break down protein, lipids, nucleic acids, carbohydrate and fat molecules into their simplest units  group of physiologically active lipid compounds having diverse hormone-like effects  peptides, acts as immunomodulating agents  e.g. Interleukin-1 (IL-1) that activates T-lymphocytes, IL-6, IL-8, interferon (IFN) & tumour necrosis factor (TNF) II- Natural killer cells(NKCs)  large granular lymphocytes (LGL),  a distinct subset of cytotoxic lymphoid cells that have innate immune functions  provide rapid responses to virus-infected cell and other intracellular pathogens and respond to tumor formation contain small granules in their cytoplasm contain proteins such as and proteases known as causing the death of the infected cell by (forms pores in the cell membrane) or (programed cell death) III- Dendritic cells (DCs) also known as accessory cells)  found in an immature state in the blood  At certain development stages they grow branched projections, the dendrites that give the cell its name  present in those tissues that are in contact with the external environment, such as the skin (where there is a specialized dendritic cell type called the Langerhans cell) and the inner lining of the nose, lungs, stomach and intestines.  Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system (antigen presenting cells APCs). They act as messengers between the innate and the adaptive immune systems.  Antigen-presenting cells (APCs) o Cells whose main function is (antigen presentation). o APCs process antigens and present them to T-cells - cell surface proteins expressed by most human cells - present both self and non self antigen T- helper cells bound to recognize these Antigen processed a MHC molecule complexes using their T cell receptors macrophages, B cells and dendritic cells, can present antigens Present the antigens to T- helper cells originating inside the cell to cytotoxic T cells. Eosinophils – acidophils  granulocytes that develop during hematopoiesis in the bone marrow  Contain large acidophilic cytoplasmic granules  combating multicellular parasites e.g. helminthes,  control mechanisms associated with allergy and asthma Basophils  the least common type of granulocytes  develop during hematopoiesis in the bone marrow  they are susceptible to staining by basic dyes,  responsible for: inflammatory reactions during immune response, the formation of acute and chronic allergic diseases, including anaphylaxis, asthma, atopic dermatitis and hay fever. Mast cells  Mast cells are originated from pluripotent progenitor cells of the bone marrow,  Under normal conditions, mature mast cells do not circulate in the bloodstream.  the cell progenitors migrate into tissues and differentiate into mast cells present throughout the body  play important roles in the maintenance of many physiological functions as well as in the pathophysiology of diseases. The complement system   also known as complement cascade, it is a part of the immune system  number of small proteins (and protein fragments ) that are synthesized by the liver  circulate in the blood as inactive precursors. Complement activation:  Complement system is stimulated (activated) by one of several triggers  proteases in the system cleave specific proteins to release cytokines and initiate an amplifying cascade of further cleavages. Through two pathways. The classical pathway The alternative pathway immunologic Non- immunologic Non- immunologic immunologic activation activation activation activation Ig G &Ig M C – Reactive Protein Endotoxins. Ig A binding with Tyrosine – like enzymes. Polysaccharides the first Some viruses. Yeast cell walls complement Some Bacteria Trypsin like component enzymes (C1) an Ag-Ab complex. The Biological Significance of Complement Activation: Enhancement of antigen presentation Chemotaxis and activation of leukocytes and mast cells Opsonization of microorganisms for phagocytosis Pathogens lysis Clearance of immune complexes Anaphylatoxins activate mast cells & basophils directly causing release of histamine & other mediators of inflammation.  Adaptive – acquired Immunity Cells of adaptive immunity (Lymphocytes). - originate, during haematopoiesis. , from a common lymphoid progenitor - The formation of lymphocytes is known as lymphopoiesis B cells (B for bursa in birds, B cells T cells migrate to and mature in mature in the bursa of Fabricius, ) the thymus mature in the bone marrow  Highly specific immune response with sequential steps: A- Presentation B- Recognition Via antigen presenting cells Specific T- lymphocytes recognize antigens as Self-antigens Non self antigens normally does not activate T Cell tolerance C- Activation & proliefration Two outcomes of this process the creation of T-cell populations antigen-specific antibody production by B cells Cell-Mediated Immunity Antibody (Humoral Immunity) primary defense against viruses and fungi act against bacterial infections and Tumor cells toxic foreign substances delayed hypersensitivity reactions Cell-Mediated Immunity Different T- Cell populations and functions: Differentiation Creation of Groups of A- Presentation specific, differentiated T B- Recognition cell subtypes (T- Cell Populations) have a C- activation & variety of important functions in controlling Proliferation and shaping the immune response  All T- lymphocytes express surface molecule CD (cluster of designation or classification determinant) according to the type of the CD the cells are classified and named - Activate macrophages - Stimulate the B cell to differentiate CD4 T - - Attract and activate eosinophils helper - Secrete cytokines - Induce IgE production (allergy) - proliferateand become cytotoxic CD-8 T - Eventually leading to lysis of the Cytotoxic T cells infected or transformed host cell T- regulatory- - Shut down T cell–mediated immunity toward suppressor the end of an immune reaction - to suppress autoreactive T cells that express CD-25 potentially self-reactive antigen receptors Memory T cells - Remember what happen allow for more rabid CD 62 response Humoral Immunity Immunoglobulins- Antibodies production A- Presentation B- Recognition Differentiation C- activation &Proliferation Of the progeny cells in to Plasma Cells Memory Cells (Effectors) survive in the body Produce to enable long- Immunoglobulins- lasting immunity to Antibodies the antigen.  antibodies are released into the blood and tissue fluids, as well as many secretions. Because these fluids were traditionally known as humors, antibody-mediated immunity is sometimes known as, or considered a part of, humoral immunity. There are five main known classes of immunoglobulins Igs: M - A - G - E - D MAGED Ig M.  Produced chiefly during the body’s primary response to a foreign antigen.  activation of complement  formation of immune complexes (aggregates of antibody, antigen, and complement)  Mostly is occur intravascular Ig A.  defends external body surfaces and is present in saliva, tears, nasal fluids, and respiratory, GI, and genitourinary secretions. IgG. constitutes 75% of the serum immunoglobulins crosses the placenta, giving protection to the newborn. Ig E. is involved in the release of vasoactive amines stored in basophils and tissue mast cell granules, causing the allergic effects Ig D present in serum in minute amounts, is the predominant antibody found on the surface of B lymphocytes and serves mainly as an antigen receptor.  It may function in controlling lymphocyte activation or suppression  Adaptive – acquired Immunity Adaptive It is the ability to discriminate between different specificity antigenic epitopes and respond to those that necessitate a response (meaning that it is not a random response). - It is the ability to recall previous contact with a memory, particular antigen giving protection against it. - long-lasting or even life-long e.g. meningitis, measles. - is absent at birth Acquired - respond to previously unseen antigen which may never have existed before.  adaptive immune response Primary Secondary  Initial antigen recognition  same antigen a second time  the subsequent adaptive immune  the sensitized specific T- and response B-cell clones become antigen- specific memory cells,  peak at 7 to 10 days  peaks at 3 to 5 days  adaptive immune response Artificial Natural Vaccination Active Active Passive Passive Ags ener the Ags introduced Prepared body naturally Abs from the in to the body performed Abs the body mother to produces Abs introduced in to produce Abs feotus through and activate the body and activte placental lymphocyte lymphcyets barrier